Families located through a proband with presenile dementia will be investigated along genetic lines. The probands come from a series of 2,254 autopsies done on relatively unselected psychiatric patients. The primary aims are to estimate the genetic contribution to the etiology of the presenile dementias and to further refine their classification using clinical, pathological, and genetic evidence. In addition, the use of Minnesota State morbidity and mortality data will make possible limited but useful estimates of epidemiologic parameters. Families of favorable composition for studies of genetic linkage, and for analysis of brain and serum proteins, and for seeking evidence of viral infection will be further investigated. Long term clinical follow-up, especially of families likely to illustrate problems in genetic counseling will be done.